Effect of antiviral therapy combined with interferon on negative conversion rate of surface antigen among patients of chronic hepatitis B treated with nucleos(t)ide analogues

doi:10.3877/cma.j.issn.1674-1358.2019.04.003

Abstract

Abstract:

Objective

To investigate the effect of antiviral therapy combined with interferon on negative conversion rate of surface antigen in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues.

Methods

From January 2014 to January 2018, a total of 75 patients with CHB treated with NAs were selected from Beijing Ditan Hospital, Capital Medical University. All the patients with HBV DNA < 100 IU/ml and HBsAg < 1 000 IU/ml were divided into two groups: NAs continued treatment group (37 cases) and NAs combination with IFN group (38 cases) according to the patient’s willingness to accept the interferon treatment. The patients were treated for 48 weeks. The serum level of HBsAg decreased at 24 weeks, the rate of HBsAg negative at 48 weeks and the related predictors of HBsAg negativity were observed in both groups, respectively.

Results

In the NAs combination with IFN group (27 cases: among the 38 cases, 1 case was eliminated and 10 cases had not been followed up), the percentage of HBsAg clearance was 48.15% (13/27) and the HBsAg seroconversion rate was 44.44% (12/27), while in NAs continued treatment group (37 cases), both of the two percentages were 5.41% (2/37), with significant differences (χ² = 13.599, P < 0.001; χ² = 11.730, P = 0.001). The level of HBsAg of patients in NAs combination with IFN group decreased gradually with the prolongation of the treatment period. At the 24th week, patients in NAs combination with IFN group, the average level of quantitative HBsAg was 15.49 (0.06, 358.39) IU/ml, HBsAg decreased for 52.77 (6.29, 203.60) IU/ml compared with the level at baseline and the percentage of HBsAg decrease > 0.5 log₁₀IU/ml was 56.76% (21 cases). However, patients in NAs continued treatment group, the average level of quantitative HBsAg was 578.82 (53.29, 778.76) IU/ml, HBsAg decreased by 31.54 (-14.43, 59.29) IU/ml compared with the level at baseline and the percentage of HBsAg decrease > 0.5 log₁₀IU/ml was 8.11% (3 cases), all with significant differences (Z =-3.850, P < 0.001; Z =-3.000, P = 0.003; χ² = 17.822, P < 0.001). Multivariate Logistics regression analysis showed that the decrease of HBsAg at baseline HBsAg, the 24th > 0.5 log₁₀IU/ml was correlated with the negative conversion of HBsAg at the 48th week of treatment in patients with CHB who were effectively controlled by HBV DNA and with low level of HBsAg after treatment with NAs.

Conclusions

After NAs treatment, CHB patients of HBV DNA effectively controlled and low HBsAg level treated by combination of NAs and IFN could promote the decrease of HBsAg level and increase the negative conversion rate of HBsAg.

Key words: Hepatitis B, Clinical cure, Combination therapy, HBsAg negative rate

Shan Zhang, Yixuan Wang, Jing Sun, Lin Zhu, Fengshui Wang, Huichun Xing. Effect of antiviral therapy combined with interferon on negative conversion rate of surface antigen among patients of chronic hepatitis B treated with nucleos(t)ide analogues[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2019, 13(04): 273-280.

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References 23

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临床指标	原方案治疗组（37例）	联合治疗组（38例）	统计量	P值
性别（男/女）	25/12	29/9	χ² = 1.096	0.295
年龄（ ± s，岁）	43.2 ± 11.7	38.9 ± 9.8	t =－1.727	0.088
HBsAg（IU/ml）^a	560.09（83.22，755.11）	206.24（51.31，675.05）	Z =－1.141	0.254
HBeAg（S/CO）^a	0.52（0.31，5.89）	0.52（0.32，1.94）	Z =－0.057	0.955
HBeAg（+/－，例）	11/21	11/24	χ² = 0.066	0.798
WBC（ ± s，× 10⁹/L）	5.72 ± 1.57	5.82 ± 1.55	t = 0.291	0.772
RBC（ ± s，× 10¹²/L）	4.82 ± 0.53	4.95 ± 0..49	t = 1.205	0.232
HBG（ ± s，g/L）	148.56 ± 16.35	151.51 ± 15.34	t = 0.789	0.432
PLT（ ± s，× 10⁹/L）	169.27 ± 80.40	192.78 ± 65.41	t = 1.361	0.178
ALT（U/L）^a	21.60（13.75，27.95）	19.00（14.00，39.05）	Z =－0.876	0.381
AST（U/L）^a	22.50（18.80，25.45）	20.20（17.40，26.75）	Z =－0.492	0.623

临床指标	原方案治疗组（37例）	联合治疗组（38例）	统计量	P值
性别（男/女）	25/12	29/9	χ² = 1.096	0.295
年龄（ ± s，岁）	43.2 ± 11.7	38.9 ± 9.8	t =－1.727	0.088
HBsAg（IU/ml）^a	560.09（83.22，755.11）	206.24（51.31，675.05）	Z =－1.141	0.254
HBeAg（S/CO）^a	0.52（0.31，5.89）	0.52（0.32，1.94）	Z =－0.057	0.955
HBeAg（+/－，例）	11/21	11/24	χ² = 0.066	0.798
WBC（ ± s，× 10⁹/L）	5.72 ± 1.57	5.82 ± 1.55	t = 0.291	0.772
RBC（ ± s，× 10¹²/L）	4.82 ± 0.53	4.95 ± 0..49	t = 1.205	0.232
HBG（ ± s，g/L）	148.56 ± 16.35	151.51 ± 15.34	t = 0.789	0.432
PLT（ ± s，× 10⁹/L）	169.27 ± 80.40	192.78 ± 65.41	t = 1.361	0.178
ALT（U/L）^a	21.60（13.75，27.95）	19.00（14.00，39.05）	Z =－0.876	0.381
AST（U/L）^a	22.50（18.80，25.45）	20.20（17.40，26.75）	Z =－0.492	0.623

组别	例数	HBsAg（IU/ml）^a		HBsAg阴转率[例（%）]^b	HBsAg下降> 0.5 log₁₀IU/ml [例（%）]^b
组别	例数	治疗24周时	治疗24周下降程度	HBsAg阴转率[例（%）]^b	HBsAg下降> 0.5 log₁₀IU/ml [例（%）]^b
原方案治疗组	37	578.82（53.29，778.76）	31.54（－14.43，59.29）	1（2.7）	3（8.11）
联合治疗组	37	15.49（0.06，358.39）	52.77（6.29，203.60）	9（24.32）	21（56.76）
统计量	?	Z =－3.850	Z =－3.000	χ² = 5.666	χ² = 17.822
P值	?	< 0.001	0.003	0.017	< 0.001

组别	例数	HBsAg（IU/ml）^a		HBsAg阴转率[例（%）]^b	HBsAg下降> 0.5 log₁₀IU/ml [例（%）]^b
组别	例数	治疗24周时	治疗24周下降程度	HBsAg阴转率[例（%）]^b	HBsAg下降> 0.5 log₁₀IU/ml [例（%）]^b
原方案治疗组	37	578.82（53.29，778.76）	31.54（－14.43，59.29）	1（2.7）	3（8.11）
联合治疗组	37	15.49（0.06，358.39）	52.77（6.29，203.60）	9（24.32）	21（56.76）
统计量	?	Z =－3.850	Z =－3.000	χ² = 5.666	χ² = 17.822
P值	?	< 0.001	0.003	0.017	< 0.001

组别	例数	HBsAg阴转率	血清学转换率
原方案治疗组	37	2（5.41）	2（5.41）
联合治疗组	27	13（48.15）	12（44.44）
χ²值	?	13.599	11.730
P值	?	< 0.001	0.001

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